JP2020073585A - Wrinkle improver - Google Patents

Abstract

To provide a wrinkle improver in which a natural product-derived compound having a wrinkle improvement action is found, out of natural product-derived compounds, and the compound is used as an active principle.SOLUTION: In the invention, as an active principle of the wrinkle improver, glycyrrhizinic acid dipotassium, is used.SELECTED DRAWING: None

Description

  The present invention relates to a wrinkle improving agent containing a compound derived from a natural product as an active ingredient.

  The epidermis and dermis of the skin are composed of epidermal cells, fibroblasts, and extracellular matrices such as collagen and elastin which are outside these cells and support the skin structure. Proliferation of fibroblasts is active in young skin, and by maintaining the homeostasis of the interaction between skin tissue such as fibroblasts and extracellular matrix components, flexibility and elasticity are secured, and the skin looks It is also maintained in tension and luster.

  However, when it is affected by some external factors such as irradiation with ultraviolet rays, remarkable drying of air, excessive skin washing, or aging progresses, collagen, elastin, etc., which are the main constituents of the extracellular matrix, Its production decreases, and it causes decomposition and deterioration. As a result, the flexibility and elasticity of the skin are reduced, the skin loses its tension and luster, and aging symptoms such as wrinkles are exhibited.

  A wide variety of components have been proposed as components for suppressing the formation of wrinkles and components for improving wrinkles (see, for example, Patent Documents 1 and 2), but at present the demand for new active ingredients is still great. is there.

JP, 09-255548, A JP, 2005-0085571, A

  An object of the present invention is to find compounds having a wrinkle improving action from compounds derived from natural products, and to provide a wrinkle improving agent containing the compound as an active ingredient.

  In order to solve the above problems, the wrinkle improving agent of the present invention is characterized by using dipotassium glycyrrhizinate as an active ingredient.

  According to the present invention, by using dipotassium glycyrrhizinate as an active ingredient, it is possible to provide a wrinkle improving agent having excellent action and effect.

Hereinafter, embodiments of the present invention will be described.
The wrinkle improving agent of the present embodiment contains dipotassium glycyrrhizinate as an active ingredient.

  Dipotassium glycyrrhizinate can be obtained by reacting glycyrrhizinate with potassium hydroxide (KOH), etc., and glycyrrhizinate can be obtained by isolating and purifying from a plant extract containing glycyrrhizinate. .. Incidentally, the plant extract containing glycyrrhizinic acid, an extract obtained by using a plant containing glycyrrhizinic acid as an extraction raw material, a diluent or concentrate of the extract, a dried product obtained by drying the extract, Alternatively, any of these crudely purified products or purified products is included.

  A plant extract containing glycyrrhizic acid can be obtained by a method generally used for extracting plants. Examples of the plant containing glycyrrhizic acid include licorice and the like.

  Licorice is a perennial herb belonging to the genus Glycyrrhiza of the legume family. For licorice, Glychyrrhiza glabra, Glychyrrhiza inflata, Glychyrrhiza uralensis, Glychyrrhiza pulary alypa, Glychyrrhiza pallah, lypa, Glychyrrhiza inflata. ), Glychyrrhiza yunnanensis, Glychyrrhiza lepidota, Glychyrrhiza echinata, Glychyrrhiza acanthocarpa, and many other types of these, including Glychyrrhiza acanthocarpa. Licorice of Glychyrrhiza uralen may be used as an extraction raw material, but especially Glychyrrhiza glabra and Glychyrrhiza uralen sis) and Glychyrrhiza inflata are preferably used as the extraction raw material.

  As a constituent part of licorice that can be used as an extraction raw material, a root part, an underground part such as a rhizome, or a mixture of these parts is usually used.

  The extract from the above plant can be obtained by drying the extraction raw material, pulverizing it as it is or using a coarse crusher, and subjecting it to extraction with an extraction solvent. Drying may be performed in the sun or using a commonly used dryer. Further, it may be used as an extraction raw material after pretreatment such as degreasing with a non-polar solvent such as hexane. By performing the pretreatment such as degreasing, the extraction treatment with the polar solvent can be efficiently performed.

  As the extraction solvent, it is preferable to use a polar solvent, and examples thereof include water, hydrophilic organic solvents, and the like. These are used alone or in combination of two or more, and are used at room temperature or a temperature not higher than the boiling point of the solvent. Preferably.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those that have been subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present embodiment also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  Hydrophilic organic solvents that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.

  When a mixed solution of two or more polar solvents is used as the extraction solvent, the mixing ratio can be adjusted appropriately. For example, when a mixed solution of water and lower aliphatic alcohol is used as an extraction solvent, the mixing ratio of water and lower aliphatic alcohol is preferably 9: 1 to 1: 9 (volume ratio), It is more preferably 7: 3 to 2: 8 (volume ratio). When a mixed solution of water and lower aliphatic ketone is used, it is preferable that the mixing ratio of water and lower aliphatic ketone is 9: 1 to 2: 8 (volume ratio). When a mixed liquid with a polyhydric alcohol is used, the mixing ratio of water and polyhydric alcohol is preferably 5: 5 to 1: 9 (volume ratio).

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in 5 to 15 times (mass ratio) the amount of the extraction raw material (mass ratio), the soluble component is extracted at room temperature or under heating under reflux, and then extraction is performed by removing the extraction residue. A liquid can be obtained. The solvent is distilled off from the obtained extract to obtain a paste-like concentrate, and the concentrate is further dried to obtain a dry product.

  The method for isolating and purifying dipotassium glycyrrhizinate from the extract obtained as described above, the concentrate of the extract or the dried product of the extract is not particularly limited, and may be performed by a conventional method. You can For example, the extract is dissolved in a developing solvent and subjected to column chromatography using a porous material such as silica gel or alumina, a porous resin such as styrene-divinylbenzene copolymer or polymethacrylate, and dipotassium glycyrrhizinate. And a method of collecting a fraction containing In this case, the developing solvent may be appropriately selected according to the stationary phase to be used. For example, when the extract is separated by normal phase chromatography using silica gel as the stationary phase, the developing solvent is chloroform: methanol = 95: 5 and the like. Further, the fraction containing dipotassium glycyrrhizinate obtained by column chromatography is optionally subjected to reverse-phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, column chromatography using an ion exchange resin, or the like. You may refine | purify using the organic compound refining means of.

  Dipotassium glycyrrhizinate can be obtained by reacting the glycyrrhizinate thus obtained with potassium hydroxide (KOH) or the like by a conventional method.

  The dipotassium glycyrrhizinate obtained as described above has an excellent wrinkle-improving action, and thus can be used as an active ingredient of a wrinkle-improving agent. The wrinkle improving agent of this embodiment can be used for a wide range of applications such as pharmaceuticals, quasi drugs, and cosmetics.

  The wrinkle-improving agent of the present embodiment may be composed of dipotassium glycyrrhizinate alone, or may be a preparation of dipotassium glycyrrhizinate. In the case of formulation, a pharmaceutically acceptable carrier such as dextrin or cyclodextrin and any other auxiliaries are used in accordance with a conventional method to prepare an arbitrary dosage form such as powder, granules, tablets and liquid. Can be converted. At this time, as the auxiliary agent, for example, an excipient, a binder, a disintegrating agent, a lubricant, a stabilizer, a flavoring agent, a flavoring agent and the like can be used. The wrinkle improving agent can be used by being blended with other compositions (for example, skin cosmetics described later), and can also be used as an ointment, an external preparation, a patch and the like.

  When the wrinkle improving agent of the present embodiment is formulated, the content of dipotassium glycyrrhizinate is not particularly limited and can be appropriately set according to the purpose.

  The wrinkle-improving agent of the present embodiment can be used as an active ingredient by blending with another potassium natural extract having a wrinkle-improving effect together with dipotassium glycyrrhizinate.

  Examples of the method for administering the wrinkle improving agent of the present embodiment to a patient include transdermal administration and oral administration. Depending on the type of disease, a method suitable for prevention / treatment thereof may be appropriately selected. Also, the dose of the wrinkle improving agent of the present embodiment may be appropriately increased or decreased depending on the type of disease, severity, individual difference of patient, administration method, administration period and the like.

  The wrinkle-improving agent of the present embodiment has an excellent wrinkle-improving action, and thus is suitable for incorporation into, for example, an external preparation for skin and food and drink. In this case, the wrinkle improving agent to be blended may be dipotassium glycyrrhizinate as it is, or may be formulated from dipotassium glycyrrhizinate.

Here, the external preparation for skin is not limited in its category, and includes a wide range of quasi-drugs, pharmaceuticals, etc. used transdermally, in addition to the skin cosmetics described below.
In addition, the food and drink is not limited in its category, and broadly includes general foods orally ingested, health foods (functional foods and drinks), foods with health claims (foods for specified health uses, foods with nutritional claims), etc. ..

  The wrinkle-improving agent according to the present embodiment exhibits an excellent wrinkle-improving action based on the action of dipotassium glycyrrhizinate, and is therefore suitable for incorporation in skin cosmetics. In this case, as the wrinkle improving agent to be blended, dipotassium glycyrrhizinate may be blended as it is, or one prepared from dipotassium glycyrrhizinate may be blended. By adding the above-mentioned wrinkle improving agent, it is possible to impart a wrinkle improving action to the skin cosmetic, and it becomes particularly suitable as a skin cosmetic.

  The type of skin cosmetics in which the wrinkle improving agent of the present embodiment can be blended is not particularly limited, and examples thereof include ointments, creams, emulsions, lotions, lotions, gels, beauty oils, packs, foundations and the like. ..

  When the above-mentioned wrinkle improving agent is added to the skin cosmetics, the amount thereof can be appropriately adjusted according to the type of the skin cosmetics, but the preferable mixing ratio is about 0. 0 in terms of dipotassium glycyrrhizinate. It is 0001 to 10% by mass, and a particularly preferable blending ratio is about 0.001 to 1% by mass.

  The skin cosmetic is a main agent, an auxiliary agent or other component used in the production of ordinary skin cosmetics, for example, an astringent, a bactericidal / antibacterial agent, a whitening agent, as long as it does not hinder the wrinkle improving action of dipotassium glycyrrhizinate. , UV absorbers, moisturizers, cell activators, anti-inflammatory / anti-allergic agents, antioxidants / active oxygen scavengers, oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances Etc. can be used together. Such combined use results in a more general product, and synergistic action with other combined active ingredients may bring about superior effects beyond those normally expected.

  The wrinkle improving agent of the present embodiment improves wrinkles of the skin through the action of dipotassium glycyrrhizinate as an active ingredient, and can suppress the formation of wrinkles, whereby the aging of the skin based on the formation of wrinkles. The symptoms can be ameliorated, and the aging symptoms of the skin due to the formation of wrinkles can be prevented or treated.

Since the wrinkle-improving agent of the present embodiment has an excellent wrinkle-improving action, it can be suitably used as a reagent for research on these action mechanisms.
The wrinkle-improving agent of the present embodiment is preferably applied to humans, but animals other than humans (eg, mouse, rat, hamster, dog, It can also be applied to cats, cattle, pigs, monkeys, etc.).

  Hereinafter, the present invention will be specifically described with reference to formulation examples and test examples, but the present invention is not limited to the following examples. The dipotassium glycyrrhizinate used in the following formulation examples is a commercial product (manufactured by Maruzen Pharmaceutical Co., Ltd.).

[Formulation Example 1]
A lotion was produced by a conventional method according to the following composition.
Dipotassium glycyrrhizinate 0.5% by mass
POE / POP decyl tetradecyl ether 0.10% by mass
Xanthan gum 0.50% by mass
Citric acid 0.04% by mass
Sodium citrate 0.16% by mass
Disodium edetate 0.03 mass%
Phenoxyethanol 0.30% by mass
Paraoxybenzoic acid ester 0.15% by mass
Purified water balance (total amount is 100% by mass)

[Comparative formulation example 1]
A lotion was produced in the same manner as in Formulation Example 1 except that dipotassium glycyrrhizinate was not blended.

[Test Example] Wrinkle improving action test Using the lotions of Formulation Example 1 and Comparative Formulation Example 1 obtained as described above, the wrinkle improving action was tested as follows.

  Twenty females aged 30 to 60 years old having similar wrinkles on the left and right outer corners of the eyes were selected as subjects. Those who have factors (skin inflammation, eczema, trauma, etc.) that may affect the test results on the skin at the evaluation site; cosmetic medicine (botox injection, hyaluronic acid, etc.) that affects the evaluation site. Those who have undergone collagen injection, photofacial, etc.) were excluded from the subjects.

  Each test subject was applied with the lotion of Formulation Example 1 on one side of the left and right outer corners of the eye, and the lotion of Comparative Formulation Example 1 on the other side twice a day, about 2 drops each time for 4 weeks. It was It was randomly assigned to each subject whether to apply both lotions to the left or right.

Replicas were collected on the test start date and 4 weeks after the test start, and evaluated by two-dimensional image analysis using oblique illumination. That is, after washing the face, after acclimatizing for 20 minutes or more in an environmental test room (room temperature 21 ° C., humidity 50%), a replica was collected using a replica agent (product name “SILFLO”, manufactured by Flexico). About the obtained replica, the main analysis area is a square with a side of 10 mm, which is about 5 mm away from the external canthus to the outside of the face. Was analyzed. For the analysis, a wrinkle area ratio (%) was evaluated by using a replica analysis system for reflection ASA-03RXD and reflection type three-dimensional skin analysis software Version 3.45 (manufactured by Asahi Biomed). Regarding the obtained results, a paired t-test was performed for the intra-group comparison between the test start date and 4 weeks after the test start, and the inter-group comparison of the change amount from the test start date to 4 weeks after the test start. ..
The results are shown in Table 1.

As shown in Table 1, in the application site of Formulation Example 1, a tendency of a decrease was observed 4 weeks after the start of the test as compared with the test start date (change amount: -0.5% ± 1.2). %, P = 0.098).
Further, comparing the application site of the formulation example 1 with the application site of the comparative formulation example 1, the application site of the formulation example (-0.5% ± 1. 2%) and the application site of Comparative Formulation Example 1 (0.3% ± 1.5%), a significant difference (p = 0.012) was observed.
Therefore, in the formulation group 1 (composition of dipotassium glycyrrhizinate) applied group, it was recognized that the wrinkles around the corners of the eyes were improved in comparison before and after the test period and in comparison with the comparative formulation example 1 applied group.

[Formulation Example 2]
A milky lotion was produced according to the following composition by a conventional method.
Dipotassium glycyrrhizinate 0.01g
Jojoba oil 4.00g
1,3-butylene glycol 3.00 g
Arbutin 3.00g
Polyoxyethylene cetyl ether (20E.O.) 2.50g
Olive oil 2.00g
Squalane 2.00g
Cetanol 2.00 g
Glyceryl monostearate 2.00 g
Polyoxyethylene sorbitan oleate (20E.O.) 2.00g
Methyl paraoxybenzoate 0.15g
Yellow frost extract 0.10 g
Ginkgo biloba extract 0.10g
Conchiolin 0.10g
Oat extract 0.10g
Chamomile extract 0.10g
Fragrance 0.05g
Purified water balance (total amount is 100 g)

[Formulation Example 3]
A cream having the following composition was produced by a conventional method.
Dipotassium glycyrrhizinate 1.0 g
Kujin extract 0.1g
Ougon Extract 0.1g
Liquid paraffin 5.0 g
White beeswax 4.0g
Squalane 10.0g
Cetanol 3.0g
Lanolin 2.0g
Stearic acid 1.0g
Polyoxyethylene sorbitan oleate (20E.O.) 1.5g
Glyceryl monostearate 3.0 g
Oil-soluble licorice extract 0.1g
1,3-butylene glycol 6.0 g
Methyl paraoxybenzoate 1.5g
Perfume 0.1g
Purified water balance (total amount is 100 g)

[Formulation Example 4]
A beauty essence having the following composition was produced by a conventional method.
Dipotassium glycyrrhizinate 0.1g
Chamomile extract 0.1g
Carrot extract 0.1g
Xanthan gum 0.3g
Hydroxyethyl cellulose 0.1g
Carboxy vinyl polymer 0.1g
1,3-butylene glycol 4.0 g
Glycerin 2.0g
Potassium hydroxide 0.25g
Fragrance 0.01g
Preservative (methyl paraoxybenzoate) 0.15g
Ethanol 2.0g
Purified water balance (total amount is 100 g)

  The wrinkle-improving agent of the present invention can greatly contribute to the improvement of skin aging symptoms due to the formation of wrinkles.

Claims (1)

  A wrinkle improving agent comprising dipotassium glycyrrhizinate as an active ingredient.